While too little stress can lead to boredom and depression,
too much can cause anxiety and poor health. The right amount of acute stress,
however, tunes up the brain and improves performance and health.
“You always think
about stress as a really bad thing, but it’s not,” said Daniela Kaufer,
associate professor of integrative biology at the University of California,
Berkeley. “Some amounts of stress are good to push you just to the level of
optimal alertness, behavioural and cognitive performance.”
New research by Kaufer and UC Berkeley post-doctoral fellow
Elizabeth Kirby has uncovered exactly how acute stress – short-lived, not
chronic – primes the brain for improved performance.
How the research was
In studies on rats, they found that significant, but brief
stressful events caused stem cells in their brains to proliferate into new
nerve cells that, when mature two weeks later, improved the rats’ mental
“I think intermittent stressful events are probably what
keeps the brain more alert, and you perform better when you are alert,” she
Kaufer, Kirby and their colleagues in UC Berkeley’s Helen
Wills Neuroscience Institute describe their results in a paper published April
16 in the new open access online journal eLife.
The UC Berkeley researchers’ findings, “in general,
reinforce the notion that stress hormones help an animal adapt – after all,
remembering the place where something stressful happened is beneficial to deal
with future situations in the same place,” said Bruce McEwen, head of the
Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology at The
Rockefeller University, who was not involved in the study.
Stress and the brain
Kaufer is especially interested in how both acute and
chronic stress affect memory, and since the brain’s hippocampus is critical to
memory, she and her colleagues focused on the effects of stress on neural stem
cells in the hippocampus of the adult rat brain. Neural stem cells are a sort
of generic or progenitor brain cell that, depending on chemical triggers, can
mature into neurons, astrocytes or other cells in the brain.
The dentate gyrus of the hippocampus is one of only two
areas in the brain that generate new brain cells in adults, and is highly
sensitive to glucocorticoid stress hormones, Kaufer said.
Brain cells called
astrocytes (pink) appear to be key players in the response to acute stress.
Stress hormones stimulate astrocytes to release fibroblast growth factor 2
(green), which in turn lead to new neurons (blue). Image by Daniela Kaufer
& Liz Kirby.
Much research has demonstrated that chronic stress elevates
levels of glucocorticoid stress hormones, which suppresses the production of
new neurons in the hippocampus, impairing memory. This is in addition to the
effect that chronically elevated levels of stress hormones have on the entire
body, such as increasing the risk of chronic obesity, heart disease and
Less is known about the effects of acute stress, Kaufer
said, and studies have been conflicting.
To clear up the confusion, Kirby subjected rats to what, to
them, is acute but short-lived stress – immobilization in their cages for a few
hours. This led to stress hormone (corticosterone) levels as high as those from
chronic stress, though for only a few hours. The stress doubled the
proliferation of new brain cells in the hippocampus, specifically in the dorsal
Kirby discovered that the stressed rats performed better on
a memory test two weeks after the stressful event, but not two days after the
event. Using special cell labelling techniques, the researchers established
that the new nerve cells triggered by the acute stress were the same ones
involved in learning new tasks two weeks later.
“In terms of survival, the nerve cell proliferation doesn’t
help you immediately after the stress, because it takes time for the cells to
become mature, functioning neurons,” Kaufer said. “But in the natural
environment, where acute stress happens on a regular basis, it will keep the
animal more alert, more attuned to the environment and to what actually is a
threat or not a threat.”
They also found that nerve cell proliferation after acute
stress was triggered by the release of a protein, fibroblast growth factor 2
(FGF2), by astrocytes — brain cells formerly thought of as support cells, but
that now appear to play a more critical role in regulating neurons.
hexagons), a glucocorticoid hormone related to stress, stimulates astrocytes to
release FGF2, which triggers the generation of new neurons from neural stem
“The FGF2 involvement is interesting, because FGF2
deficiency is associated with depressive-like behaviors in animals and is
linked to depression in humans,” McEwen said.
Acute stress harmful
Kaufer noted that exposure to acute, intense stress can
sometimes be harmful, leading, for example, to post-traumatic stress disorder.
Further research could help to identify the factors that determine whether a
response to stress is good or bad.
“I think the ultimate message is an optimistic one,” she
concluded. “Stress can be something that makes you better, but it is a question
of how much, how long and how you interpret or perceive it.”
The eLife paper was coauthored by UC Berkeley colleagues
Sandra E Muroy, Wayne G. Sun and David Covarrubias of the Department of
Molecular and Cell Biology; Megan J. Leong of the Helen Wills Neuroscience
Institute; and Laurel A. Barchas of the Department of Integrative Biology.
Kirby is now a post-doctoral fellow at Stanford University.
Kaufer’s research was funded by a BRAINS (Biobehavioral
Research Awards for Innovative New Scientists) award from the National
Institute of Mental Health of the National Institutes of Health (R01 MH087495)
and the National Alliance for Research on Schizophrenia and Depression. Kirby
was supported by fellowships from the California Institute for Regenerative
Medicine and the U.S. Department of Defense.